Opioid receptors are the target receptors of specific binding by drugs with morphine-like activity, and such receptors are present in the central nervous system and enteric nervous system. Three types of opioid receptors are known, μ, δ and κ. The opioid μ receptors are associated with analgesia, respiratory depression, euphoria, psychosomatic dependence, tolerance, enterokinetic inhibition, bradycardia, constipation and miosis. On the other hand, the opioid δ receptors are associated with analgesia, psychosomatic dependence and emotion, while opioid κ receptors are associated with analgesia, sedation, bradycardia, diuresis, aversion and miosis.
WO03/035645 describes 4-(2-furoyl)aminopiperidine derivatives which act as opioid μ receptor antagonists. Because this group of compounds exhibit strong opioid μ receptor antagonism and are selective for peripheral regions, they are useful as therapeutic agents for enterokinetic disorders such as constipation and irritable bowel syndrome. However, although the group of compounds exhibit powerful opioid μ receptor antagonism and have been effective against the side-effects of opioid μ receptor agonists such as constipation, nausea and vomiting, or against idiopathic constipation, postoperative ileus, paralytic ileus and irritable bowel syndrome, they have either failed to produce any effect or a satisfactory effect against itching or pruritus, and therefore more powerful therapeutic agents for itching or pruritus have been desired. US Patent Publication US2003-004340A also teaches that compounds that bind to opiate receptors (for example, μ, κ and δ receptors) are useful for treatment of itching or pruritus.